The Roles of Transcription Factor GATA2 in T Cell Development by Epigenetic Memory

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19537
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Tohoku University
• Principal Investigator: Harigae Hideo 東北大学, 医学系研究科, 教授 (50302146)
• Co-Investigator(Kenkyū-buntansha): 加藤 浩貴 東北大学, 大学病院, 講師 (50801677)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: GATA2 / T細胞初期分化

Outline of Final Research Achievements

GATA2 is a transcription factor that is essential for the maintenance and differentiation of hematopoietic stem cells. Genetic mutation of GATA2 can be a cause of GATA2 deficiency syndrome, and its severe case shows T cell development impairments, suggesting the notion that GATA2 might possess important roles for T cell development. However, still little is known about the roles of GATA2 in T cell development. In this study, we sought to reveal the roles of GATA2 in T cell development. We found that the earliest T cell progenitors in the thymus express GATA2 at a comparable level of lymphoid progenitors in the bone marrow. Taking advantage of comprehensive transcriptomic analysis and open chromatin analysis revealed that GATA2 might possess significant roles in the earliest T cell progenitors in the thymus to regulate its survival and differentiation potentials.

Free Research Field

造血

Academic Significance and Societal Importance of the Research Achievements

今回の研究から、これまで不明な点の多かった、T細胞の初期分化における、造血幹細胞のマスター転写因子GATA２の働きの一端が明らかとなった。特に、胸腺における最も未熟な細胞をGATA２の発現量に基づいて規定できる可能性があると同時に、この細胞こそが自然免疫細胞と獲得免疫細胞の最終分化の分岐点である可能性が考えられ、造血における細胞の運命決定機構を理解する上で、今後欠かせない発見であると考えられる。